Journal Article Epublish 1 citation
PubMed: 41281896 DOI: 10.1016/j.bbih.2025.101124
Functional olfactory impairment and fatigue in post-COVID-19 syndrome including ME/CFS - a longitudinal prospective observational study.
Brain Behav Immun Health 50:101124
Authors: Lil Meyer-Arndt, Greta Pierchalla, Lukas Mödl, Felix Wohlrab, Franziska Legler, Uta Hoppmann, Claudia Kedor, Kirsten Wittke, Helma Freitag, Frank Konietschke, Heidi Olze, Friedemann Paul, Carmen Scheibenbogen, Judith Bellmann-Strobl, Ulrike Förster-Ruhrmann
Affiliations
- Experimental and Clinical Research Center, A Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, 13125, Berlin, Germany.
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany.
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, BIH Charité Junior Clinician Scientist Program, 10117, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Department of Neurology and Experimental Neurology, 10117, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Otorhinolaryngology, CCM and CVK, 10117, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, 10117, Berlin, Germany.
- Experimental and Clinical Research Center, A Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Germany. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, 13125, Berlin, Germany. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany.
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, 13353, Berlin, Germany.
Abstract
Post-COVID-19 syndrome (PCS) affects a significant proportion of individuals, with olfactory impairment and fatigue as prominent long-term symptoms. A subset of PCS patients with pronounced fatigue meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), here referred to as PCS-ME/CFS. This study explores the relationship between PCS, fatigue, and olfactory function, and investigates the potential of olfactory impairment as a diagnostic and prognostic marker. We assessed olfactory function up to 28 months post-COVID-19 in 45 PCS patients (22 PCS, 23 PCS-ME/CFS) using the extended Sniffin' Sticks test, which evaluates odor threshold, discrimination, and identification, providing a composite score. Fatigue severity and health-related quality of life were assessed using validated questionnaires, a standardized test measured cognitive function, and handgrip strength indicated physical fatiguability. Both PCS and PCS-ME/CFS patients showed significant improvement in olfactory function, with all patients returning to normosmia after 20 months, regardless of diagnosis. While odor threshold was the most affected olfactory measure in Sniffin' Sticks testing, odor identification was the only measure that remained impaired over time. Olfactory impairment correlated with cognitive, physical, and mental performance, with stronger correlations in the PCS group, particularly linking better odor discrimination at baseline to improved daily functioning and health-related quality of life after 20 months. Our findings suggest that odor identification assessed in standardized testing may remain impaired the longest in patients with persisting symptoms after COVID-19, reflecting persisting central processing difficulties. Correlations between olfactory performance, cognitive function, and physical ability point to shared underlying mechanisms. Early olfactory improvements may be linked to better long-term cognitive outcomes, highlighting a possible prognostic role of olfactory function in these patients.
MeSH
Research Design, Quality Of Life, Fatigue Syndrome, Chronic, Signs And Symptoms, Covid-19, Fatigue, Cognition